Abstract 3915: Novel Drug-delivery System for Oral Curcumin That Prevents Systolic Function Deterioration After Myocardial Infarction in Rats
Purpose: While nuclear acetylation is being recognized as a critical event during myocardial cell hypertrophy, pharmacological heart failure therapy that targets this pathway has yet to be established. Recently, we found that curcumin (Cur), a natural compound that inhibits p300 histone acetyltransferase activity, prevents the deterioration of the systolic function in two different rat models of heart failure, hypertension and myocardial infarction (MI). While we administered 50 mg/kg/day of Cur to rats, Cur is absorbed barely and most of the oral dose passes through the gastro-intestinal tract. To achieve efficient oral pharmacological therapy for heart failure using Cur, we have established a novel Cur drug-delivery system (DDS) that increases plasma Cur levels.
Methods: We generated a Cur-containing drug using an emulsifying agent which contains gum ghatti. Rats were subjected to a sham operation or MI. One week later, we performed left ventricular (LV) functional studies by employing echocardiography involving all surviving rats. The rats with a moderate area of MI (fractional shortening (FS) <40%) were then randomly assigned to 3 groups:
gum ghatti (vehicle control) (n=12),
native Cur (0.5 mg/kg/day, n=12),
Cur in gum ghatti (DDS Cur, 0.5 mg/kg/day, n=12).
Oral treatments with these agents were repeated everyday and continued for 6 weeks.
Results: There were no differences among the 3 groups in all LV geometric and functional data examined before the treatment. After treatment, LVFS was significantly (p<0.05) greater in group III (26.0±0.9%) than in group I (13.8±0.7%) or II (14.1±0.9%). The LV wall thickness was significantly thinner in group III (1.3±0.2 mm) than in group I (2.6±0.2 mm) or II (2.3±0.2 mm). There were no biochemical or hematological abnormalities in blood samples from all rat groups. We found that the plasma concentration of Cur was 60-fold higher in rats orally administered DDS Cur than those given native Cur.
Conclusions: Orally administering a low dose of DDS Cur, but not that of native Cur, improves post-MI LV systolic dysfunction in rats. Thus, this novel DDS of Cur may be useful in long-term pharmacological therapy for heart failure in the clinical setting.
This research has received full or partial funding support from the American Heart Association, National Center.